19-52365964-T-C

Variant names:

• chr19-52365964-T-C
• NM_001161425.2:c.586T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001161425.2(ZNF610):​c.586T>C​(p.Tyr196His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y196N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF610 NM_001161425.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.76

Genes affected

ZNF610 (HGNC:26687): (zinc finger protein 610) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06586021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF610	NM_001161425.2	c.586T>C	p.Tyr196His	missense_variant	Exon 6 of 6	ENST00000403906.8	NP_001154897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF610	ENST00000403906.8	c.586T>C	p.Tyr196His	missense_variant	Exon 6 of 6	1	NM_001161425.2	ENSP00000383922.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.586T>C (p.Y196H) alteration is located in exon 6 (coding exon 4) of the ZNF610 gene. This alteration results from a T to C substitution at nucleotide position 586, causing the tyrosine (Y) at amino acid position 196 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.029
DANN	Benign	0.36
DEOGEN2	Benign	0.0036	T;T;.;T;.;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.0024	.;.;.;.;T;T
M_CAP	Benign	0.00078	T
MetaRNN	Benign	0.066	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.9	N;N;.;N;.;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.9	.;N;.;N;.;.
REVEL	Benign	0.035
Sift	Benign	1.0	.;T;.;T;.;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0010	B;B;B;B;B;B
Vest4		0.044
MutPred		0.60		Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);.;Gain of disorder (P = 0.0308);.;Gain of disorder (P = 0.0308);
MVP		0.16
MPC		0.19
ClinPred		0.043	T
GERP RS		-3.6
Varity_R		0.028
gMVP		0.022

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52869217;